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Newly Synthesized Phosphodiesterase 4 (PDE4) Inhibitor, DWP205505, Inhibits TNF-$\alpha$ Secretion and mRNA Expression

  • Lee, Suk-Kyeong;Lee, Sun-A;Byun, Hye-Sin;Cho, Mi-La;Kim, Wan-Uk;Park, Sung-Hwan;Cho, Chul-Soo;Joo, Young-Shil;Lee, Shin-Seok;Yoo, Eun-Sook;Son, Ho-Jung;Kim, Ho-Youn
    • Journal of Microbiology and Biotechnology
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    • v.9 no.1
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    • pp.106-112
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    • 1999
  • The therapeutic potential of phosphodiesterase 4(PDE4) inhibitors in inflammatory diseases including some autoimmune diseases has been explored recently with some hopeful results. These PDE4 inhibitors are thought to show their anti-inflammatory effect by down-regulating tumor necrosis factor-a (TNF-$\alpha$) production in lymphocytes and macrophages. A high concentration of TNF-$\alpha$has been found in rheumatoid arthritis (RA) synovium and reducing TNF-$\alpha$using biological agents was proven to be an effective RA treatment. To test the possibility of using PDE4 inhibitors for RA treatment, the effects of a newly synthesized PDE4 inhibitor, DWP205505, on TNF-$\alpha$ and IL-10 production was tested in cells isolated from normal peripheral blood and rheumatoid arthritis synovial fluid. Cytokine production was assayed at the protein level by sandwich enzyme-linked immunosorbent assay (ELISA) and at the mRNA expression level by semi-quantitative RT-PCR. Another PDE4 inhibitor, RP73401, was used for comparison. DWP205505 and RP73401 had no harmful effect on cell viability up to 10 $\mu$M concentration during the 24 h culture period. DWP205505 as well as RP73401 significantly reduced TNF-$\alpha$ secretion from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (pBMC) and synovial fluid mononuclear cells (SFMC). The effect of DWP205505 or RP73401 treatment on the mRNA expression of TNF-$\alpha$ was also studied in LPS-stimulated PBMC and SFMC. TNF-$\alpha$ mRNA expression was increased by LPS stimulation and both of the PDE4 inhibitors suppressed TNF-$\alpha$ mRNA expression. For interleukin-l0 (IL-l0), a little different results were obtained from PBMC and SFMC; IL-l0 secretion was unaffected by LPS stimulation and only minimally affected by both of the PDE4 inhibitors in PBMC. In unstimulated SFMC, DWP205505 and RP73401 slightly enhanced IL-10 secretion, while they reduced IL-l0 secretion from LPS-stimulated SFMC where IL-l0 secretion was a lot higher than unstimulated SFMC. These results suggest that the newly synthesized PDE4 inhibitor DWP205505 may have anti-rheumatoid arthritis activity.

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Germinated Rhynchosia nulubilis Hydrolysate Ameliorates Dexamethasone-induced Muscle Atrophy by Downregulating MAFbx Expression in C2C12 Cells and C57BL/6 Mice (발아 서목태 가수분해물의 근위축 억제 효과)

  • Won Keong Lee;Eun Ji Kim;Sang Gon Kim;Young Min Goo;Young Sook Kil;Seung Mi Sin;Min Ju Ahn;Min Cheol Kang;Young-Sool Hah
    • Journal of Life Science
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    • v.33 no.3
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    • pp.277-286
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    • 2023
  • Sarcopenia is the age-related loss of muscle mass and function. It is a natural part of aging and can lead to decreased mobility and increased frailty. The ubiquitin-proteasome pathway, which is involved in muscle protein degradation, is closely linked to sarcopenia. Germinated Rhynchosia nulubilis hydrolysate (GRH) has been reported to have anti-inflammatory and antioxidant properties, but there have been no reports on its inhibitory effect on muscle reduction. However, no study has yet explored the relationship between GRH and muscle loss inhibition. In this study, we evaluated the effects of GRH on muscle atrophy inhibitory activity in dexamethasone (Dexa)-induced muscle atrophy C2C12 myotubes and mouse models. Moreover, we identified a molecular pathway underlying the effects of GRH on skeletal muscle. May Grunwald-Giemsa staining showed that the length and area of myotubes increased in the groups treated with GRH. In addition, the GRH-treated group significantly reduced the expression of muscle ring finger protein 1 and muscular atrophy F-box (MAFbx) in the Dexa-induced muscular atrophy C2C12 model. GRH also improved muscle strength in C57BL/6 mice with Dexa-induced muscle atrophy, resulting in prolonged running exhaustive time and increased grip strength. We found that muscle strengthening by GRH was correlated with a decreased expression of the MAFbx gene in mouse muscle tissue. In conclusion, GRH can attenuate Dexa-induced muscle atrophy by inhibiting the ubiquitin-proteasome pathway via downregulation of the MAFbx gene expression.

Comprehensive comparison of the primary and secondary metabolites and antioxidant activity of Polygoni multiflori Radix by processing methods (가공 방법에 따른 하수오의 영양성분 및 항산화 활성의 종합적인 비교)

  • Hee Yul Lee;Chung Eun Hwang;Kyung Pan Hwa;Du Yong Cho;Jea Gack Jung;Min Ju Kim;Jong Bin Jeong;Mu Yeun Jang;Kye Man Cho
    • Journal of Applied Biological Chemistry
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    • v.65 no.4
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    • pp.287-298
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    • 2022
  • This study investigated the changes in the physiochemical property, phytochemical content, nutritional content and antioxidant activity of Polygoni multiflori Radix by steam, aging, and fermentation. After processing Polygoni multiflori Radix (PMR), pH slightly decreased, while acidity increased (pH 5.70→4.78, acidity 0.23→0.29%). The reducing sugar content increased after aging and fermentation from 1.19 mg/g (PMR) to 1.40 (fermented PMR, FPMR), 1.30 (red PMR, RPMR), 1.53 (fermented red PMR, FRPMR), 1.99 (black PMR, BPMR), and 2.33 mg/g (fermented black PMR, FBPMR). Total phenolic content was highest in PMR (6.05 mg/g) and total flavonoids and maillard product were increased after aging and fermentation of PMR, and were the highest in BPMR (1.60 mg/g) and FBPMR (2.76 O.D.), respectively. The major phytochemical was 2,3,5,4'-tetrahydroxystilbene-2-0-α-glucoside, which were highest in PMR (64.9 mg/g) with 46.47 mg/g at FPMR, 33.94 mg/g at RPMR, 48.76 mg/g at FRPMR, 36.68 mg/g at BPMR and 34.35 mg/g at FBPMR. The main fatty acids and free amino acids were detected as palmitic acid (C16:0) and proline, respectively. Generally, 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical scavenging activities and FRAP reducing powers were shown high in PMR (39.06%, 98.32%, and 2.61 O.D. in extracts concentration 1.0 mg/mL), then were decreased after aging and fermentation.

Project of Improving Good Agriculture Practice and Income by Intergrated Agricultural Farming (미얀마 우수농산물 재배기술 전수사업)

  • Lee, Young-Cheul;Choi, Dong-Yong
    • Journal of Practical Agriculture & Fisheries Research
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    • v.16 no.1
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    • pp.193-206
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    • 2014
  • The objectives of the project are to increase farmers' income through GAP and to reduce the loss of agricultural produce, for which the Korean partner takes a role of transferring needed technologies to the project site. To accomplish the project plan, it is set to implement the project with six components: construction of buildings, installation of agricultural facilities, establishment of demonstration farms, dispatching experts, conducting training program in Korea and provision of equipments. The Project Management Committee and the Project Implementation Team are consisted of Korean experts and senior officials from Department of Agriculture, Myanmar that managed the project systematically to ensure the success of the project. The process of the project are; the ceremony of laying the foundation and commencing the construction of training center in April, 2012. The Ribbon Cutting Ceremony for the completion of GAP Training Center was successfully held under PMC (MOAI, GAPI/ARDC) arrangement in SAl, Naypyitaw on June 17, 2012. The Chairman of GAPI, Dr. Sang Mu Lee, Director General U Kyaw Win of DOA, officials and staff members from Korea and Myanmar, teachers and students from SAl attended the ceremony. The team carried out an inspection and fixing donors' plates on donated project machineries, agro-equipments, vehicles, computers and printer, furniture, tools and so forth. Demonstration farm for paddy rice, fruits and vegetables was laid out in April, 2012. Twenty nine Korean rice varieties and many Korean vegetable varieties were introduced into GAP Project farm to check the suitability of the varieties under Myanmar growing conditions. Paddy was cultivated three times in DAR and twice in SAl. In June 2012, vinyl houses were started to be constructed for raising seedlings and finished in December 2012. Fruit orchard for mango, longan and dragon fruit was established in June, 2012. Vegetables were grown until successful harvest and the harvested produce was used for panel testing and distribution in January 2013. Machineries for postharvest handling systems were imported in November 2012. Setting the washing line for vegetables were finished and the system as run for testing in June 2013. New water tanks, pine lines, pump house and electricity were set up in October 2013.

A Study on the Awareness & Preferences about the Nursing Homes (노인요양시설에 대한 고령자 인식 및 시설 내부 색채선호 경향에 관한 연구)

  • Jeong, Mu Lin;Park, Hey Kyung
    • Korea Science and Art Forum
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    • v.29
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    • pp.319-331
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    • 2017
  • South Korea has entered the age of aging society since the elderly population over 65 reached 13.1% in 2015. This increase rate is the fastest in the OECD members. as a part of the precaution, the Korean government has enforced the long term care insurance from July 2008 and the increase of related nursing homes until 2015 was 220.2% which is rapid and quantitative. It was natural that quantitative expansion leads to qualitative improvement. With regard to service environment conditions, color environment draws attention as one of the most effective measures. color environment supports nursing home's spatial functions and the aged class is subject to the research as the potential customers. This study aims to understand color environment, conduct surveys for color preference and attitude toward color environment, and suggest directions for color environment plan. The ultimate goal is to improve the quality of Korean nursing home environment. It studied definition, state, color environment and space functions of nursing homes as well as the preceding researches. With 100 people over 60s in Busan and Gyeongnam area (52 male and 48 female), the survey examined attitudes for color environment and color preference by space functions in nursing home. The research method is as follows. First, as a result of the consciousness survey on color environment in elderly nursing home, it considers service (37%), medical service (20%), and location (19%) heavily in order. color environment plan is not recognized significantly. However, the need of indoor color plan in the elderly nursing homes has "agree (32%) and "strongly agree (25%), which suggests that color introduction is required to the nursing homes. Second, the indoor coloration for the elderly nursing homes has various color preferences. The color preference order for bedroom was R, P, and G but this order changes in nursing space (program room) to G, R, and Y. The communal space such as lobby prefers R, G and Y in order. R color was preferred in general.

Contents of lead, mercury, and cadmium in seaweeds collected in coastal area of Korea (국산 해조류의 납, 수은 및 카드뮴 함량)

  • Hwang, Young Ok;Kim, Mu Sang;Park, Seog Gee;Kim, Su Jeong
    • Analytical Science and Technology
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    • v.20 no.3
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    • pp.227-236
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    • 2007
  • This study was carried out to estimate the contents of heavy metals (Hg, Pb, and Cd) in seaweeds (n=169) which are closely related to food resources. The contents of heavy metals in the laver were found as follows; Hg was highly detected in the east coastal area ($0.0509{\pm}0.0635mg/kg$), Pb in the south coastal area ($0.0509{\pm}0.0635mg/kg$), Cd in the south coastal area ($1.3785{\pm}0.7754mg/kg$). In the sea mustard, Hg was highly detected in the south coastal area ($0.0152{\pm}0.0116mg/kg$), Pb in the east coastal area ($0.1633{\pm}0.2888mg/kg$), Cd in the south coastal area ($0.7141{\pm}0.4952mg/kg$). In the sea tangle, Hg was highly detected in the south coastal area ($0.0177{\pm}0.0118mg/kg$), Pb in the east coastal area ($0.0728{\pm}0.1025mg/kg$), Cd in the south coastal area ($0.1640{\pm}0.1253mg/kg$). In the sea lettuce, Hg, Pb, and Cd were highly detected from the west coastal area. In the fusiforme, Hg and Cd were highly in the west coastal area, Pb in the south coastal area. In general brown algae showed the highest level of Hg, Pb, and green algae showed the highest level of Cd Additionally, the significant correlation was observed between Hg and Cd (r=0.513, p<0.01), between Cd and Pb (r=0.420, p<0.05). The weekly average intakes of Hg, Pb and Cd from seaweeds takes about 0.17~10.30 % of PTWI (Provisional Tolerable Weekly Intakes) that FAO/WHO Joint Food Additive and Contaminants Committee has set to evaluate their safeties.

Evaluation of Antimicrobial Activities of Rhubarb Extracts on Putrefactive Microorganisms Related to Soybean Curd (Doobu) (두부 부패 미생물에 대한 대황(Rhubarb) 추출물의 항균 활성 평가)

  • Kim, Chul-Jai;Suh, Hee-Ji;Chung, Hee-Sook
    • Journal of the Korean Society of Food Culture
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    • v.21 no.2
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    • pp.225-231
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    • 2006
  • 대황(Rhubarb)은 중국과 일본에서 혈액 순환제, 진통제, 신장치료제 등으로 전통적으로 사용되고 있는 약용식물이다. 이 연구에서는 한국산 R. undulatum L.의 뿌리 추출물, 미국산 R. rhabarbarum L.과 중국산 R. palmatum L.의 줄기 추출물의 두부 부패에 관여하는 미생물에 대한 항균 활성을 평가하였다. Rhubarb의 최적 추출을 위해서 각각 50%, 70%, 80% 에탄올을 용매로 사용하였으며, 항균 활성은 Kirby-Bauert test, minimum inhibitory concentration (MIC)과 minimum bactericide concentration (MBC)에 의해서 평가되었다. Kirby-Bauert test 결과, R. undulatum L.의 뿌리 추출물은 대부분 두부 부패균에 대해서 항균 활성을 가지는 것으로 나타났으며, R. rhabarbarum L.의 줄기 추출물의 경우는 $20{\mu}g/disc$의 농도에서는 항균 활성이 거의 나타나질 않았으나, 고농도로 갈수록 높은 항균 활성을 나타내었다. 또한 R. palmatum L.의 줄기 추출물은 고농도로 갈수록 항균 활성이 높아졌으나, Pseudomonas aeruginosa에 관해서는 항균 활성이 나타나지 않았다. MIC와 MBC에 의한 항균 활성 평가실험에서는, 세 종류의 rhubarb 추출물 중에서 phenolic 화합물이 가장 많이 함유되어 있는 R. undulatum L.의 뿌리 추출물보다 R. rhabarbarum L.의 줄기 추출물이 MIC와 MBC 값이 낮았다. 이는 phenolic 화합물의 양 이외에 낮은 pH가 항균 활성에 영향을 준 것으로 판단된다. 본 연구를 통해서 rhubarb 추출물은 두부 부패에 관여하는 미생물에 대해서 항균 활성을 가지는 것으로 나타났으며, 천연 항균제로써 식품에 적용 가능성이 있는 것으로 평가되었다. 87.1%이었으며, 아침을 매일 먹는 채식남학생은 78.8%, 비채식남학생은 33.3%, 채식여학생 47.1%, 비채식여학생 39.6%이었다. 또한 식사의 양은 과식한다는 응답이 채식남학생 24.2%, 비채식남학생 38.1%, 채식여학생은 29.4%, 비채식여학생 40.6%으로 비책식군의 과식율이 높았다. 5. 식품 섭취빈도는 두부 및 콩제품을 매일 섭취하는 경우는 채식남학생 54.6%, 비채식남학생 16.7%, 채식여학생은 38.2%, 비채식여학생이 16.8%이었다. 우유 및 유제품을 매일 섭취하는 경우는 채식남학생 6.1%, 비채식남학생 33.3%, 채식여학생 14.7%, 비채식여학생은 21.8%이었으며, 녹차, 커피 등 차를 마시지 않는다는 비율은 채식남학생 69.7%, 비채식남학생 28.6%, 채식여학생 29.4%, 비채식여학생 25.7%이었다. 인스턴트 식품을 매일 섭취한다는 응답율이 채식남학생 9.1%, 비채식남학생 21.4%, 채식여학생은 17.7%, 비채식여학생은 14.9%이었다. 6. 운동, 체중 조절 등에 대한 조사 결과 항상 운동을 하는 경우는 채식남학생 30.3%, 비채식남학생 28.6%, 채식여학생 14.7%, 비채식여학생 18.8%이었으며 운동시간은 $1{\sim}2$시간 하는 경우는 채식남학생 30.3%, 비채식남학생 38.1%, 채식여학생은 8.8%, 비채식여학생은 17.8%이었다. 체중에 만족하는 정도를 보면 채식남학생 57.6%, 비채식남학생 23.8%, 채식여학생은 23.5%, 비채식여학생은 15.8%가 만족한다고 하였다. 체중 조절 경험에서 경험이 있는 경우가 채식남학생 3.0%, 비채식남학생 31.0%, 채식여학생은 23.5%, 비채식여학생 31.7%이었다. 7. 골밀도 BQI값과와 몇가지 요인의 상관관계를 살펴보았을때, 채식남학생은 영양보충제의 섭취와 유의적인 양의 상관관계를, 해조류의 섭취정도와 유의적인 음의 상관관계를 나타내었다.

Embryonic and Larval Development of Slender Catfish, Silurus microdorsalis Mori, 1936, Endemic to Korea (한국 고유종 미유기(Silurus microdorsalis Mori, 1936)의 난 발생 및 자치어 형태발달)

  • Kang-Rae Kim;Yeong-Ho Kwak;Mu-Sung Sung;Heon Yang;Seong-Jang Cho;Bong Han Yun;In-Chul Bang
    • Korean Journal of Ichthyology
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    • v.35 no.2
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    • pp.91-100
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    • 2023
  • The early life history of Silurus microdorsalis living in Jahocheon Stream was studied by observing egg and morphological development. Live fish were captured in June 2018, then reared in a circulating filtration system under a 14L : 10D photoperiod with a water temperature of 18℃. To artificially induce spawning, females were injected with 0.5 mL of Ovaprim (Syndel, Nanaimo, BC, Canada) per kg of body weight, and males were injected with 10,000 IU/kg body weight of human chorionic gonadotropin. Approximately 15 h later, eggs were artificially inseminated by the dry method. Mature eggs were light pale yellow, which separated them from immature eggs. Fertilized eggs were 2.16±0.06 mm (n=8) in diameter and fully hatched at 181 h after fertilization. The fertilization rate was 63.1±2.2%, and 10.0±3.7% of the embryos were malformed at 18℃. The rates of development were 181 h at 18℃, 109 h at 21℃, and 76 h at 24℃. The larval size immediately after hatching was 4.64±0.22 mm (n=8), and the larvae displayed negative phototaxis at 1 day after hatching. The total larval length on 7 days after hatching was 12.47±0.53 mm, with 25~30 basal anal fin rays and 14~16 basal caudal fin rays observed. The total larval length was 14.13±0.51 mm on 9 days after hatching, and approximately 90% of the black endoplasmic reticulum was deposited on the head and body. The dorsal fin had formed, and a single basal body was observed. On 15 days after hatching, the total larval length was 16.69±0.31 mm; the number of basal caudal fin rays (18 poles) was an integer because 2 dorsal fin basal rays and 60~63 anal fin basal rays were observed. The total larval length was 28.96±1.10 mm on 50 days after hatching; the numbers of caudal fins (n=18), dorsal fins (n=3), pectoral fins (n=11), and anal fin basal rays (n=67~73) were integers.

A Study on the Origin of Human Governance Periods in the Hidden Stems (인원용사(人元用事)의 연원에 관한 연구)

  • Won-Ho Choi;Na-Hyun Kim;Ki-Seung Kim
    • Industry Promotion Research
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    • v.9 no.1
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    • pp.203-212
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    • 2024
  • The purpose of this study is to examine the validity of Hidden Stems (支藏干) in the Four Pillars of Destiny with regard to the use of human governance periods in the hidden stems (人元用事). First, there is a theory of assigning period of governance for designated constituents (司令論) in the Hidden Stems of the Earthly Branch. Second, there is a theory that determines the structure of the Four Pillars by the Exposed Constituent from the Hidden Stems (透出論) in the Month Earthly Branch. Since these two theories conflict with each other and cause confusions, this study examined the theory of Hidden Stems in the Four Pillars Classics and examined the historical development of governance period for constituent hidden stems and their validity. The results of the study are as follows: Firstly, the number of dates assigned to respective constituents does not correspond to the calendarical principle, and the assignment of the governance dates for each constituent does not correspond to the principles proposed in ancient books of Four Pillars. Second, though it is said in the Classics that 72 days are equally assigned to each of the Five Elements, actual distributed days for the five elements was 65 days for Wood, 55 days for Fire, 100 days for Earth, 65 days for Metal, and 65 days for Water. Third, though it is said that 7 days should be designated to Yang Earth Mu for the months of Tiger 寅, Monkey, Snake, and Pig, it is logically more legitimate to assign those days to Yin Earth Ki since the month before Tiger is Ox, and the month before Monkey is Goat. Lastly, rationale behind assigning Ki Earth only to Horse Oh as constituting Hidden Stem while disregarding months of Rat, Rabbit, and Rooster is considered not reasonable. Looking at these results comprehensively, it is concluded that the Exposed Constituent theory is logically more appropriate than Assigned Governance theory.

Traumatic Hemothorax Caused by Thoracic Wall and Intrathoracic Injuries: Clinical Outcomes of Transcatheter Systemic Artery Embolization (흉벽 및 흉곽 내 장기 손상으로 인한 외상성 혈흉: 전신 동맥 색전술의 임상 결과)

  • Chang Mu Lee;Chang Ho Jeon;Rang Lee;Hoon Kwon;Chang Won Kim;Jin Hyeok Kim;Jae Hun Kim;Hohyun Kim;Seon Hee Kim;Chan Kyu Lee;Chan Yong Park;Miju Bae
    • Journal of the Korean Society of Radiology
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    • v.82 no.4
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    • pp.923-935
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    • 2021
  • Purpose We aimed to assess the clinical efficacy of transcatheter arterial embolization (TAE) for treating hemothorax caused by chest trauma. Materials and Methods Between 2015 and 2019, 68 patients (56 male; mean age, 58.2 years) were transferred to our interventional unit for selective TAE to treat thoracic bleeding. We retrospectively investigated their demographics, angiographic findings, embolization techniques, technical and clinical success rates, and complications. Results Bleeding occurred mostly from the intercostal arteries (50%) and the internal mammary arteries (29.5%). Except one patient, TAE achieved technical success, defined as the immediate cessation of bleeding, in all the other patients. Four patients successfully underwent repeated TAE for delayed bleeding or increasing hematoma after the initial TAE. The clinical success rate, defined as no need for thoracotomy for hemostasis after TAE, was 92.6%. Five patients underwent post-embolization thoracotomy for hemostasis. No patient developed major TAE-related complications, such as cerebral infarction or quadriplegia. Conclusion TAE is a safe, effective and minimally invasive method for controlling thoracic wall and intrathoracic systemic arterial hemorrhage after thoracic trauma. TAE may be considered for patients with hemothorax without other concomitant injuries which require emergency surgery, or those who undergoing emergency TAE for abdominal or pelvic hemostasis.